Seifert Michael E, Mannon Roslyn B
Department of Pediatrics, University of Alabama at Birmingham School of Medicine, Birmingham, AL.
Department of Medicine, University of Alabama at Birmingham School of Medicine, Birmingham, AL.
Clin Transpl. 2015;31:211-225.
Despite dramatic improvements in acute rejection rates and short-term allograft survival, long-term allograft survival remains unchanged in the modern era, largely due to chronic allograft injury, a progressive disease that is common across all solid organ transplantation but has no proven treatment. Studies of novel diagnostic and therapeutic strategies for chronic allograft injury have been relatively sparse, in part due to the time and expense required to conduct traditional long-term clinical studies of a variably progressive disease. In this article, we review the pathophysiology of chronic allograft injury, including recent insights into key mechanisms of the disease. We discuss the barriers to progress in chronic allograft injury research and present alternative approaches to study design that could accelerate improvements in diagnosis, prevention, or treatment of the disease. We integrate these approaches with emerging biomarkers and surrogate endpoints into a model clinical study of chronic renal allograft injury, providing a framework for modern study design in solid organ transplantation.
尽管急性排斥反应率和短期移植器官存活率有了显著提高，但在现代，长期移植器官存活率仍未改变，这主要归因于慢性移植器官损伤，这是一种在所有实体器官移植中都很常见的进行性疾病，但尚无经证实的治疗方法。针对慢性移植器官损伤的新型诊断和治疗策略的研究相对较少，部分原因是开展对一种进展程度不一的疾病进行传统长期临床研究所需的时间和费用。在本文中，我们回顾了慢性移植器官损伤的病理生理学，包括对该疾病关键机制的最新见解。我们讨论了慢性移植器官损伤研究进展的障碍，并提出了研究设计的替代方法，这些方法可以加速疾病诊断、预防或治疗方面的改善。我们将这些方法与新兴的生物标志物和替代终点整合到一项慢性肾移植器官损伤的典型临床研究中，为实体器官移植的现代研究设计提供了一个框架。
